Letters Serum Lipoprotein (a) as a Risk Factor for Extracranial Carotid Artery Atherosclerosis In their multivariate analysis of the effect of serum lipoproteins on extracranial carotid artery atherosclerosis in the March 1991 issue ofthe Mayo ClinicProceedings(pages 259267), Homer and associates did not report on measuring serum lipoprotein (a) [Lp(a)]. This "low-density lipoprotein-like" particle contains, in addition to apoprotein B-1OO, the unique glycoprotein apolipoprotein (a).' Discovery of the striking structural homology between apolipoprotein (a) and human plasminogen' has stimulated intensive investigation of Lp(a) as a possible "link" between atherosclerosis and thrombosis. I •2 Recent studies have shown that Lp(a) can bind fibrin, inhibit tissue plasminogen activator-fibrin binding, suppress plasminogen activation by tissue plasminogen activator, and competitively inhibit plasminogen binding to monocytoid cells, endothelial cells, tetranectin, and thrombospondin." This in vitro evidence of interference with normal fibrinolytic mechanisms supports a role for Lp(a) in promoting thrombosis. Native Lp(a) and recombinant apolipoprotein (a) can bind to macrophages through a specific high-affinity receptor;' the result is the intracellular accumulation of cholesterol. These data demonstrate a mechanism for formation of atheromatous foam cells by Lp(a), in addition to its thrombogenic potential. Certain case-control studies'> and a recent prospective study" have established Lp( a) as an independent risk factor for angiographically determined coronary atherosclerosis and myocardial infarction. Since 1985, five additional studies>? have suggested that Lp(a) is an independent risk factor for extracranial carotid artery atherosclerosis or cerebral infarction. Koltringer and Jurgens" reported that Lp(a) was a more powerful predictor of the presence, extent, and thrombotic progression of extracranial carotid artery atherosclerosis, as assessed by Doppler and B-mode ultrasonography, than either hypertension or smoking. Despite these findings, we agree with Homer and colleagues that previous investigations of the relationship between lipoproteins and extracranial carotid artery atherosclerosis, including studies of serum Lp(a), had methodologic inadequacies. The use of discordant methods for assessing atherosclerosis and the lack of multivariate regression analyses have been the most glaring shortcomings in these reports. Interestingly, a recent sizable study" that used a multiple logistic regression model found comparable odds ratios for risk of stroke with increased levels of serum Lp( a) or a history ofhypertension. The odds ratio for smoking was substantially Mayo Clin Proc 67:303-306, 1992

lower than that for either increased concentration of serum Lp(a) or hypertension, and smoking was not an independent risk factor for stroke in the multiple regression analysis. This study did not evaluate the relationship between these risk factors and extracranial carotid artery atherosclerosis. We are unaware of any studies that have directly examined the relationship between serum concentration of Lpta) and angiographically determined extracranial carotid artery atherosclerosis. We suggest that future angiographic data bases, such as the one compiled by Homer and co-workers, should include measurement of Lp(a) to elucidate its role as a risk factor for extracranial carotid artery atherosclerosis. Andrew G. Bostom, M.D. Department of Medicine

J. Donald Easton, M.D. Department of Neurology Rhode Island Hospital Providence, Rhode Island

REFERENCES 1. MBewu AD, Durrington PN: Lipoprotein (a): structure, properties and possible involvement in thrombogenesis and atherogenesis. Atherosclerosis 85:1-14,1990 2. Miles LA, Plow EF: Lp(a): an interloper into the fibrinolytic system? Thromb Haemost 63:331-335,1990 3. Zioncheck TF, Powell LM, Rice GC, Eaton DL,Lawn RM: Interaction of recombinant apolipoprotein(a) and Iipoproteinf a) with macrophages. J Clin Invest 87:767-771, 1991 4. Rosengren A, Wilhelmsen L, Eriksson E, Risberg B, Wedel H: Lipoprotein (a) and coronary heart disease: a prospective casecontrol study in a general population sample of middle aged men. BMJ 301:1248-1250,1990 5. Koltringer P, Jurgens G: A dominant role oflipoprotein (a) in the investigation and evaluation of parameters indicating the development of cervical atherosclerosis. Atherosclerosis 58: 187198, 1985 6. WooJ,LauE,LamCWK,KayR, TeohR, Wong HY, PrallWY, Kreel L, Nicholls MG: Hypertension, lipoprotein(a), and apolipoprotein A-I as risk factors for stroke in the Chinese. Stroke 22:203-208, 1991 7. Zenker G, Koltringer P, Bone G, Niederkorn K, Pfeiffer K, JUrgens G: Lipoprotein(a) as a strong indicator for cerebrovascular disease. Stroke 17:942-945, 1986 8. JUrgensG, Koltringer P: Lipoprotein(a) in ischemic cerebrovascular disease: a new approach to the assessment of risk for stroke. Neurology 37:513-515, 1987 9. Murai A, Miyahara T, Fujimoto N, Matsuda M,Kameyama M: Lp(a) lipoprotein as a risk factor forcoronary heart disease and cerebral infarction. Atherosclerosis 59:199-204,1986

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Serum lipoprotein (a) as a risk factor for extracranial carotid artery atherosclerosis.

Letters Serum Lipoprotein (a) as a Risk Factor for Extracranial Carotid Artery Atherosclerosis In their multivariate analysis of the effect of serum l...
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